Platinum binding to metallothionein. Analysis of circular dichroism spectra of complexes formed between metallothionein and platinum from cis- and trans-diamminedichloroplatinum

Abstract

The first observation of the circular dichroism (CD) spectral features of platinum-saturated metallothionein, Pt7MT, is presented. It is characterized by two intensive bands with maxima at 235 nm (-) and 255 nm (+). Properties of the reactions of cis- and trans-diamminedichloroplatinum (DDP) with rabbit liver MT have been studied by monitoring the CD spectral changes. The overall rate of the reaction between trans-DDP and MT is determined to be significantly faster than that for cis-DDP and MT. The stepwise incorporation of Pt into Zn7MT resulted in a nonsystemic changes in the CD spectral envelope. These data argue that Pt(II) replaces Zn(II) in ZnMT in a nonspecific, "distributed" manner across both domains, because the onset of clustering was observed after 5 mol equiv of Pt was bound. A dynamic mechanism has been proposed in which the reaction proceeds via the formation of an intermediate, RS-Pt (NH3)2-SR. As it is converted to the product, the ammine ligands are lost very slowly, especially in the case of cis-DDP, because of the strong requirement of Pt for square planar coordination, which comprises the rate-limiting step.